Cell
Volume 71, Issue 3, 30 October 1992, Pages 383-390
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Article
Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development

https://doi.org/10.1016/0092-8674(92)90508-AGet rights and content

Abstract

The myogenic basic HLH transcription factor family of genes, composed of MyoD, myogenin, Myf-5, and Myf-6, are thought to regulate skeletal muscle differentiation. To understand the role of MyoD in myogenesis, we have introduced a null mutation of MyoD into the germline of mice. Surprisingly, mice lacking MyoD are viable and fertile. Histological examination of skeletal muscle failed to reveal any morphological abnormalities in these mice. Furthermore, Northern analysis revealed normal levels of skeletal muscle-specific mRNAs. Significantly, Myf-5 mRNA levels are elevated in postnatal mutant mice. Normally, Myf-5 expression becomes markedly reduced at day 12 of gestation when MyoD mRNA first appears. This suggests that Myf-5 expression is repressed by MyoD. Our results indicate that MyoD is dispensable for skeletal muscle development in mice, revealing some degree of functional redundancy in the control of the skeletal myogenic developmental program.

References (48)

  • K.R. Thomas et al.

    Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells

    Cell

    (1987)
  • W.E. Wright et al.

    Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD

    Cell

    (1989)
  • J.D. Bancroft et al.

    Theory and Practice of Histological Techniques

    (1990)
  • N.E. Block et al.

    Expression of Mrf4, a myogenic helix-loop-helix protein, produces multiple changes in the myogenic program of BC3H-1 cells

    Mol. Cell. Biol.

    (1992)
  • A. Bradley

    Production and analysis of chimaeric mice

  • T. Braun et al.

    Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products

    EMBO J.

    (1989)
  • T. Braun et al.

    A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T12 fibroblasts

    EMBO J.

    (1989)
  • T. Braun et al.

    Myf-6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12

    EMBO J.

    (1990)
  • T. Braun et al.

    Inhibition of muscle differentiation by the adenovirus E1a protein: repression of the transcriptional activating function of the HLH protein Myf-5

    Genes Dev.

    (1992)
  • T. Braun et al.

    Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal distal rib development snd early postnatal death in homozygous mouse mutants

    Cell

    (1992)
  • M. Buckingham

    Making muscle in mammals

    Trends Genet.

    (1992)
  • J.N. Buskin et al.

    Identification of a myocyte-specific nuclear factor which binds to the muscle-specific enhancer of the mouse creatine kinase gene

    Mol. Cell. Biol.

    (1989)
  • L. Chen et al.

    Body-wall muscle formation in Caenorhabditis elegans embryos that lack the MyoD homolog hIh-1

    Science

    (1992)
  • M. Donoghue et al.

    A muscle-specific enhancer is located at the 3′ end of the myosin light chain 13 locus

    Genes Dev.

    (1988)
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    Present address: Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada, L8S 4K1.

    §

    Present address: Biology Research Laboratories, Takeda Chemical Industries, LTD, Yodokowa-Ku, Osaka 532, Japan.

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